This invention relates generally to methods and apparatus for non-invasive determination of the concentration of particular constituents of a patient's blood. In particular, the invention determines the concentration of constituents such as glucose, and other clinical analytes without providing an external radiation source. The invention can be utilized to measure the concentration of such analytes both in clinical settings and also at home, e.g., home glucose testing.
The non-invasive determination of various constituents of blood provides distinct advantages over traditional invasive procedures. The invasive techniques expose patients to various contaminants in the environment which can potentially lead to contracting diseases such as AIDS or hepatitis B if adequate safety precautions for the use of the invasive methods are not taken. Non-invasive techniques eliminate such potentially harmful exposures and can play important roles in the management of many patients, e.g., diabetic patients. Diabetic patients who need to monitor the glucose content of their blood on a regular basis, typically several times a day, have traditionally employed the finger prick technique for obtaining a blood sample. This technique is not only painful but it also exposes such patients to contaminants in the environment. Patients with artificial heart valves comprise another group of individuals who need to monitor the concentration of various constituents of their blood. For example, such patients may require monitoring of particular constituents in order to properly adjust the intake level of blood-thinning medication. Accordingly, all these individuals can benefit from a non-invasive technique for measuring the concentration of various constituents of blood that is safe and easy to use.
Many issued patents disclose the use of radiation for the non-invasive determination of the glucose concentration of blood. For example, U.S. Pat. No. 3,958,560 discloses an apparatus for the non-invasive measurement of the glucose content of a patient's blood. The disclosed apparatus scans the patient's eye by using a source of radiation located at one side of the patient's cornea and detects the radiation after it passes through the cornea by a sensor located on the other side. The intensity of the transmitted radiation is then correlated to the concentration of glucose. U.S. Pat. No. 4,014,321 discloses a non-invasive glucose sensing device that employs a polarized source of infrared radiation, and correlates the level of glucose in the cornea of a patient to the degree of the rotation of the plane of polarization of the radiation as it passes through the cornea.
The limitations of the invasive techniques in combination with a heightened sense of concern in regard to spread of diseases such as AIDS, have led to a resurgence of interest in developing non-invasive optical techniques in the past several years. For example, U.S. Pat. No. 5,028,787 of Rosenthal et al. discloses a non-invasive apparatus for measuring the glucose content of blood. In particular, Rosenthal et al. measure the intensity of IR radiation transmitted through a subject's blood at a plurality of wavelengths. Rosenthal et al.'s invention obtains the intensity of the transmitted radiation at least one pair of wavelengths, selected such that one.sub.-- is sensitive to glucose absorption and the other is not, and correlates these measurements to the concentration of glucose.
U.S. Pat. No. 5,321,265, herein incorporated by reference, discloses a non-invasive technique that employs a radiation source with a broad band spectrum in the near infrared region, e.g., 700-1100 nm, to illuminate a sample, e.g., a body part, and detects the reflected or transmitted radiation by a plurality of overlapping detection spectral responses. This invention also employs a detection system analogous to that used in color vision to create a vector whose different components relate to the measured intensity of the reflected or transmitted radiation in a particular range of wavelength.
U.S. Pat. No. 5,434,412, herein incorporated by reference, provides improvements on apparatus and methods disclosed in the aforementioned '265 patent. In particular, this patent arranges the apparatus to achieve congruent sampling, i.e., each detector receives radiation from substantially the same portion of the sample transmitted or reflected in the same direction. This results in a better signal-to-noise ratio, thus improving the accuracy of the resultant value of the concentration of the analyte of interest.
U.S. Pat. No. 5,424,545, herein incorporated by reference, employs techniques similar to those disclosed in the aforementioned '265 patent to obtain the concentration of a selected constituent of interest. It, however, differs from the '265 patent in that it employs a plurality of broad-band partially overlapping infrared radiation sources rather than a plurality of detectors with partially overlapping responses.
U.S. Pat. No. 5,666,956 discloses methods and apparatus for collecting naturally emitted thermal radiation from a body part, and for analyzing such radiation for the fingerprints of a particular analyte. In particular, the patent claims that the ratio of the emissivity of the tympanic membrane and the emissivity of a black body at the same temperature as that of the tympanic membrane can be utilized to measure the concentration of an analyte such as glucose.
U.S. Pat. Nos. 5,515,847 and 5,615,672 disclose methods and apparatus for non-invasive measurement of certain blood constituents of a subject by monitoring long-wavelength infrared radiation emitted by the subject's body, preferably from a vascularized appendage. The methods of these patents do not teach the use of a well-defined transmission sample pathlength that is optically separate and thermally isolated from the source of radiation. The accuracy and universality of the calibration of the measurement of the absolute concentration of an analyte in these patents is dependent, in part, on how well-defined is the optical pathlength of the absorbing sample. The disclosed methods do not define the value of the pathlength from where the infrared emissions originate to where they are detectable. Because the disclosed methods utilize radiation originating in a thick piece of tissue, i.e., a wrist, obtaining accurate values of the pathlength is problematic due to multiple scattering of the radiation within the tissue before reaching the detector, and also the uncertainty associated with the place within the tissue where the emitted radiation originates.
The present invention provides improvements over these and other prior art techniques for non-invasive determination of the concentration of a constituent of blood. In particular, the prior art techniques typically rely on transmission of radiation through a fairly thick piece of tissue, e.g., finger tip, which results in an attenuated intensity of transmitted radiation, thereby limiting the choice of wavelengths. Further, a majority of the disclosed non-invasive techniques employ an external radiation source to illuminate a part of a patient's body and at least a detector to measure a portion of the radiation that is transmitted through or reflected from this body part. The use of an external radiation source adds to the complexity and the expense of constructing non-invasive testing devices. In addition, many of the disclosed methods employ traditional spectroscopic analysis for obtaining the concentration of a selected constituent of blood. Although such traditional techniques are suitable for the analysis of spectra that exhibit a multiplicity of highly-resolved bands, they are not particularly appropriate for discriminating broad absorption bands, characteristic of many constituents of blood, from the background noise. In addition, the potential overlap of absorption bands of various constituents, e.g., glucose, fat, proteins, presents another difficulty for the traditional techniques.
Accordingly, it is an object of the present invention to provide methods and apparatus for the non-invasive determination of selected constituents of blood by employing either spectrally overlapping detector responses or traditional spectroscopic methods and without relying on external radiation sources.
It is another object of the invention to collect a portion of the thermal radiation that originates from a subject's inner ear after it passes through a cold segment of the tympanic membrane.
It is yet another object of the invention to take advantage of the thinness of the tympanic membrane to employ regions of spectral wavelengths not available for the measurement of constituents of blood of thicker body parts because of the opacity of these parts to such wavelengths.
It is yet another object of the present invention to provide methods and apparatus for the non-invasive determination of the concentration of selected constituents of a subject's blood by analyzing a portion of the thermal radiation emitted by the subject's inner ear that has passed through the colder tympanic membrane, thus exhibiting the spectral absorption characteristics of the subject's blood in the tympanic membrane.